The background description provided herein is for the purpose of generally presenting the context of the present invention. The subject matter discussed in the background of the invention section should not be assumed to be prior art merely as a result of its mention in the background of the invention section. Similarly, a problem mentioned in the background of the invention section or associated with the subject matter of the background of the invention section should not be assumed to have been previously recognized in the prior art. The subject matter in the background of the invention section merely represents different approaches, which in and of themselves may also be inventions. Work of the presently named inventors, to the extent it is described in the background of the invention section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as the prior art against the present invention.
In recent years, technology to combine an ion mobility spectrometer and a chromatograph-mass spectrometer in a tandem use obtains a significant development. Due to an orthogonal separation characteristic of the ion mobility spectrometry to the chromatography and mass spectrometry, the separating power and the peak capacity of chromatography-mass spectrometry analysis can be greatly improved.
For a typical drift tube ion mobility spectrometer, for example, has a 1-4 torr gas pressure, a 50-100 cm length and a 2-5 kV drift voltage across the whole length, the drift time for most ions is in a millisecond scale, and the peak width in a spectrum is in millisecond or sub-millisecond scale. If the chromatograph, ion mobility spectrometer and mass spectrometer are connected serially, the speed of the ion mobility spectrometer can totally meet the request of the chromatography which is located on the pre-stage. But the speed of mass spectrometer, which is located on the succeeding stage of the ion mobility spectrometer, needs to be operated very fast to sampling the mobility peaks, usually only a high-speed time-of-flight mass spectrometer can be used herein. For other relatively low end mass analyzer, such as quadrupole mass filter or ion trap, it takes dozens or even hundreds of milliseconds to obtain a full scan spectrum, which is too slow to couple with an ion mobility spectrometer. The time-of-flight mass spectrometer needs a high vacuum and a long flight distance. Its size is relatively large and its price is high. In addition, a typical repetition rate of a time-of-flight mass spectrometer is 5-10 kHz, even though a sampling requirement for peaks in the mobility spectrometer can be met, it generates a massive data volume, and it brings difficulty in data processing and analyzing.
In order to overcome above shortcomings, a parallel analysis between ion mobility spectrometry and mass spectrometry can be performed, which means an ion mobility spectrum and a mass spectrum of the same sample are obtained simultaneously. For a complex sample, the difficulty of such technology is how to correlate the peaks in the ion mobility spectrum to those in the mass spectrum, i.e., how to obtain the ion mobility information and corresponding m/z information for the same component (or same ion). U.S. Pat. Nos. 8,785,848, 9,024,255 and 9,142,395 disclose a parallel analysis device and method. A typical process is as below: Performing a pre-scan to obtaining the ion mobility spectrum. According to the peak position to determine the time sequence for mass spectra acquisition, usually a vacuum valve will be open or closed accordingly. The time sequence decides a corresponding relation between the mass spectrum and the ion mobility spectrum, so that both the m/z information and ion mobility information for the analytes can be obtained at the same time. The method disclosed in the patents needs synchronization firstly and needs normalization secondly, the so-called normalization refers to correlation of peaks in the mobility spectrum and peaks in the mass spectrum according to a “synchronized” time sequence. The method disclosed in the patents cannot solve all problems in the aforesaid tandem analysis. In the patents, if such a quadrupole rod or ion trap analyzer is adopted, only the target analysis on known compounds can be performed, or the mass range needs to be reduced according to the peak position in the pre-scanned mobility spectrum. From this point, the method disclosed in the patents is not a complete parallel analysis. The process of this method is similar to “data dependent acquisition”.
The so-called “data dependent acquisition (short for DDA)” or “data independent acquisition (short for DIA)” is usually applied in the field of tandem mass analysis, for example, as described in the literature, Proteomics 2015, 15, 964-980. In the DDA method, parent ions with a single m/z value are selected for collision dissociation to generate daughter ions, and then a mass analysis for those daughter ions is performed. In the DIA method, the parent ions in a certain m/z range, or even the entire range are selected, and are fed into a collision cell for dissociation to generate the daughter ions, then all daughter ions are subjected for mass analysis. A more complex data post-processing algorithm, usually called deconvolution, is necessary to correlate the daughter ions to the relevant parent ions. Compared to the DDA method, the DIA method has great superiority in its sensitivity, quantitation ability and dynamic range.
At present, the work to apply the DIA method to the ion mobility-mass spectrometry for a tandem analysis already existed. For example, there was a report in J. Proteome Res. 2013, 12, 2323-2339. In another literature, Nat. Methods 2014, 11, 167-170, it is further provided that the collision energy can be optimized according to the peak position of the mobility spectrum so as to obtain a higher dissociation efficiency to improve the qualitative and quantitative analysis capability.
But these methods are merely limited to serial (or tandem) analysis. There is no one who applies the DIA method to the ion mobility-mass spectrometry parallel analysis yet.
Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies.